Jobert Laure, Argentini Manuela, Tora László
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U 596, Université Louis Pasteur de Strasbourg, Illkirch Cedex, CU de Strasbourg, France.
Exp Cell Res. 2009 Apr 15;315(7):1273-86. doi: 10.1016/j.yexcr.2008.12.008. Epub 2008 Dec 24.
TAF15 (formerly TAF(II)68) is a nuclear RNA-binding protein that is associated with a distinct population of TFIID and RNA polymerase II complexes. TAF15 harbours an N-terminal activation domain, an RNA recognition motif (RRM) and many Arg-Gly-Gly (RGG) repeats at its C-terminal end. The N-terminus of TAF15 serves as an essential transforming domain in the fusion oncoprotein created by chromosomal translocation in certain human chondrosarcomas. Post-transcriptional modifications (PTMs) of proteins are known to regulate their activity, however, nothing is known on how PTMs affect TAF15 function. Here we demonstrate that endogenous human TAF15 is methylated in vivo at its numerous RGG repeats. Furthermore, we identify protein arginine N-methyltransferase 1 (PRMT1) as a TAF15 interactor and the major PRMT responsible for its methylation. In addition, the RGG repeat-containing C-terminus of TAF15 is responsible for the shuttling between the nucleus and the cytoplasm and the methylation of RGG repeats affects the subcellular localization of TAF15. The methylation of TAF15 by PRMT1 is required for the ability of TAF15 to positively regulate the expression of the studied endogenous TAF15-target genes. Our findings demonstrate that arginine methylation of TAF15 by PRMT1 is a crucial event determining its proper localization and gene regulatory function.
TAF15（以前称为TAF(II)68）是一种核RNA结合蛋白，与不同的TFIID和RNA聚合酶II复合物群体相关。TAF15在其N端有一个激活结构域，一个RNA识别基序（RRM），在其C端有许多精氨酸-甘氨酸-甘氨酸（RGG）重复序列。在某些人类软骨肉瘤中，由染色体易位产生的融合癌蛋白中，TAF15的N端作为一个必需的转化结构域。已知蛋白质的转录后修饰（PTM）可调节其活性，然而，关于PTM如何影响TAF15功能却一无所知。在这里，我们证明内源性人类TAF15在体内其众多RGG重复序列处发生甲基化。此外，我们鉴定出蛋白质精氨酸N-甲基转移酶1（PRMT1）是TAF15的相互作用蛋白，也是负责其甲基化的主要PRMT。另外，TAF15含RGG重复序列的C端负责在细胞核和细胞质之间穿梭，RGG重复序列的甲基化影响TAF15的亚细胞定位。PRMT1对TAF15的甲基化是TAF15正向调节所研究的内源性TAF15靶基因表达能力所必需的。我们的研究结果表明，PRMT1对TAF15的精氨酸甲基化是决定其正确定位和基因调控功能的关键事件。
